Anti-inflammatory activity of diazomethyl ketone and chloromethyl ketone analogs prepared from N-tosyl amino acids.

A series of diazomethyl ketone and chloromethyl ketone analogs prepared from N-tosyl amino acids was shown to have anti-inflammatory activity in mice at 20 mg/kg and in rats at 10 mg/kg. N-Tosyl-L-alanine and N-tosyl-beta-alanine chloromethyl ketones demonstrated the most potent anti-inflammatory activity. The writhing reflex also was inhibited at 20 mg/kg in mice. In the tail flick test, N-tosyl-D,L-alanine and N-tosyl-D,L-isoleucine chloromethyl ketones demonstrated the highest increase in time. Toxicity studies indicated good therapeutic indexes for most of these agents.